The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the expression of genes involved in Aβ generation

NEUROBIOLOGY OF AGING

卷:47

Article

Blondrath, Katrin¹  Steel, Jennifer H.²  Katsouri, Loukia¹  Ries, Miriam¹  Parker, Malcolm G.²  Christian, Mark³  Sastre, Magdalena¹ 

[1] Imperial Coll London, Dept Med, Div Brain Sci, London, England

[2] Imperial Coll London, Dept Surg & Canc, Inst Reprod & Dev Biol, London, England

[3] Univ Warwick, Warwick Med Sch, Div Metab & Vasc Hlth, Coventry, W Midlands, England

关键词: PPAR gamma;    Alzheimer's disease;    RIP140;    BACE1;    GSK3;    A beta;   

DOI  :  10.1016/j.neurobiolaging.2016.08.003

来源: Elsevier

【 摘 要 】

The receptor interacting protein-140 (RIP140) is a cofactor for several nuclear receptors and has been involved in the regulation of metabolic and inflammatory genes. We hypothesize that RIP140 may also affect A beta generation because it modulates the activity of transcription factors previously implicated in amyloid precursor protein (APP) processing, such as peroxisome proliferator-activated receptor-gamma (PPAR gamma). We found that the levels of RIP140 are reduced in Alzheimer's disease (AD) postmortem brains compared with healthy controls. In addition, in situ hybridization experiments revealed that RIP140 expression is enriched in the same brain areas involved in AD pathology, such as cortex and hippocampus. Furthermore, we provide evidence using cell lines and genetically modified mice that RIP140 is able to modulate the transcription of certain genes involved in AD pathology, such as beta-APP cleaving enzyme (BACE1) and GSK3. Consequently, we found that RIP140 overexpression reduced the generation of A beta in a neuroblastoma cell line by decreasing the transcription of beta-APP cleaving enzyme via a PPAR gamma-dependent mechanism. The results of this study therefore provide molecular insights into common signaling pathways linking metabolic disease with AD. (C) 2016 Elsevier Inc. All rights reserved.

【 授权许可】

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